TCT: Biodegradable Stent Effective at Four Years

Action Points

Explain that four-year results of the LEADERS trial found that the new biodegradable polymer stent was noninferior to the durable polymer stent for the composite outcome of cardiac death, myocardial infarction, and target vessel revascularization.

Note that the trial took place in European centers with considerable expertise in percutaneous coronary interventions which could affect generalizability.

SAN FRANCISCO -- The BioMatrix Flex stent, boasting a biodegradable polymer, was as effective as a first generation durable polymer stent after four years, researchers said here.

Four years into the LEADERS trial, the biodegradable biolimus-eluting stent was associated with fewer adverse cardiovascular outcomes than the durable sirolimus-eluting Cypher stent (P<0.0001 for noninferiority, P=0.05 for superiority), according to Thomas Ischinger, MD, PhD, of Kardiologie im Zentrum in Munich, and colleagues.

Ischinger reported the findings at the Transcatheter Cardiovascular Therapeutics meeting, and the results were simultaneously published online in The Lancet.

The benefit appears to spring largely from reductions in very late stent thrombosis, he said.

"The benefit is driven by a significant difference in favor of the biolimus-eluting stent for a lower rate of definite stent thrombosis between 12 and 48 months," Ischinger said. "These effects all occurred with similar adherence to dual antiplatelet therapy in both groups."

Drug-eluting stents have been associated with a higher risk of very late stent thrombosis compared with bare-metal stents. It's been suggested that the persistence of durable polymer material on the stent surface after the drug had been completely released could trigger a chronic inflammatory response that leads to very late stent thrombosis.

Biodegradable polymers, which dissipate after the drug has been fully released, were developed as a possible solution.

The primary, nine-month results of the LEADERS trial showed similar safety and efficacy between the biodegradable and durable polymer versions of the stents, but clinicians expected the potential for improved safety with the biodegradable form to emerge during later phases of stent implantation.

Ischinger and colleagues assessed outcomes at four years; 96% of patients in each group completed follow-up through that time point.

All 1,707 patients had coronary artery disease and had been enrolled between Nov. 27, 2006, and May 18, 2007, randomized to either a biodegradable polymer biolimus-eluting stent or durable polymer sirolimus-eluting stent.

The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularization.

Ischinger and colleagues found that at four years, the biodegradable stent was noninferior to the durable polymer in terms of the primary endpoint (18.7% versus 22.6%; RR 0.81, 95% CI 0.66 to 1.00).

The finding was significant at P<0.0001 for noninferiority, and at P=0.05 for superiority, they reported.

There was an overall lower risk of definite stent thrombosis for the biodegradable stent, but it wasn't significant. However, the diminished risk was significant for late definite thrombosis, between one and four years (RR 0.20, 95% CI 0.06 to 0.67, P=0.004).

They said the corresponding test for interaction between treatment effect and time was positive (P=0.017).

The rate of late definite stent thrombosis was 0.12% per year for the biodegradable stent versus 0.6% per year for the durable polymer stent, they found.

They also found an interaction with time for events associated with stent thrombosis -- but not for other events -- with patients receiving the biodegradable stent having more favorable outcomes, they reported.

The study was limited because the trial was conducted at 10 European centers with experienced operators and high percutaneous coronary intervention volume, so the findings may not be generalizable.

Also, the study was designed to prove noninferiority, not superiority, the researchers cautioned.

Still, Ischinger concluded that the benefit of the biodegradable stent "emerged in the later phase, and was driven by lower risk of [major adverse cardiovascular events] associated with lower rates of stent thrombosis. This provides a basis for proof-of-concept for biodegradable polymer drug-eluting stents."

In an accompanying editorial, Ron Waksman, MD, and Gabriel Maluenda, MD, of Washington Hospital Center, questioned whether the results are specific to the stents tested in LEADERS, or could be more broadly applicable to all stents in these two categories.

Other trials suggest the case may be the latter, they wrote. A meta-analysis comparing various durable polymer with biodegradable stents found similar one-year outcomes for target lesion revascularization and stent thrombosis, and three-year follow up of the ISAR-TEST-4 study found no differences between the two types of stent with respect to thrombosis or a composite endpoint of cardiac death, target vessel-related MI, or target-lesion revascularization.

Yet they cautioned that LEADERS was not designed as a superiority trial, and future trials assessing superiority of biodegradable over permanent polymer stents should have a follow-up time at least four years.

They also warned that the findings can't be extrapolated to second-generation drug-eluting stents.

Finally, the sirolimus-eluting stent Cypher is being discontinued at the end of the year.

"Although biodegradable polymer technology is scientifically appealing and the long-term results of LEADERS are encouraging," they wrote, "we are not yet in a position to confirm whether biodegradable polymers will replace durable polymer for DES technology."

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